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ChrX marker localization

The use of ChrX-STRs in kinship analysis requires knowledge of their location on the ChrX, their genetic distances, the linkage of closely located markers, and possible linkage disequilibrium. Thereby, the relationship between the genetic and physical localization of markers is not always proportional. Information about individual markers is available here via a ChrX ideogram or a linkage table. While the ideogram provides an overview over the marker distribution on the ChrX, the linkage table displays the physical (bp) and genetic (cM) localization as distance from the Xp-telomere, respectively.

Our data are based on information from the Welcome Trust Sanger Institute Human Genome Browser and the National Center for Biotechnology Information. Genetic localization can be interpolated with mapped deCODE markers or with Rutgers combined linkage-physical human genome map.

Short reports on the ChrX markers

The descriptions of the STR markers are mainly based on papers published in printed forensic journals. They include a primer proposal for each marker but no complete PCR protocols. The amplicon length refers to these primers. Allele allocations are presented together with the typical repeat structures. To enable ladder calibration, the typing results are valid for a set of reliable standard DNA i.e. K562, NA9947A, 9948 and NA3657 as recommended earlier.

Population data of STRs

Population data on ChrX STRs were collected from several papers. Although we mainly considered peer-reviewed journals, not all publications are suitable to provide data on our website because in some cases the published data do not conform to the consensus allele nomenclature of the ISFG recommendations. Such problems could be avoided if the authors generally communicated their method of allelic ladder calibration using at least two standard DNAs. Population genetic parameters such as mutation rates, PIC, PD, MEC etc. should also be reported.

Population data of haplotypes

In males, ChrX markers appear in the hemizygous state. Therefore, ChrX typing of marker clusters automatically provides haplotypes. Taking into account the crossing-over frequencies, which correlate directly with the genetic distances between the markers involved, such haplotypes can be used for kinship testing (instead of STR alleles) in certain pedigrees. Since ChrX haplotyping can generate a large amount of data, not all of them can be presented in printed journals. Therefore, a supplementary data publication beyond the printed-paper can be useful. Our website offers the possibility to publish such data online.

Submitting data for online publication

Authors can submit their published data via our web data sheet ("Submit Data" -> "Submit Data File"). We then check that the following quality standards are met:

1. Appropriate typing procedures should be used and at least two standard DNAs for ladder calibration (NA99481, NA99472, NA36571, DNA073, K562). Some of the control DNAs recommended here are included in commercial profiling kits.
2. Mutation rates should be recorded from at least 50 meioses and must be separated by maternal and paternal meiosis. The following genetic population parameters should be calculated: MEC, PIC, HET, PDfemale, PDmale. An appropriate calculation software is implemented in our website and can be used. It is also necessary to check the Hardy-Weinberg equilibrium.
3. Data on the origin of the population or a description of the appropriate ethnic group is required (e.g., European, Caucasian-American, African-American etc.).
4. The requirements for STRs also apply to haplotypes of STR clusters. However, the distance between the outermost markers of the entire cluster should not exceed a span of 5cM.

Ethical Considerations

Gonosomal aberrations

ChrX marker applications are based on regular female and male gonosomal karyotypes XX and XY. However, there are rare anomalies where this may be different.

ChrX homozygosity in females:

• Ullrich Turner syndrome: genotype X0 (female phenotype, homozygosity in all ChrX STRs)
• Testicular feminization: female phenotype and male karyotype 46,XY (no male development due to androgen receptor defect).

ChrX heterozygosity in males:

• Klinefelter syndrome: gonosomal male karyotype XXY (or other numerical aberration of ChrX)

Attention to these constellations in parentage testing is required. If such gonosomal abnormalities are detected, ChrX typing is no longer suitable for kinship testing. These are usually incidental findings and should be treated confidentially.

HumARA

We no longer consider HumARA to be a suitable DNA marker in forensic casework.

Desmarais et al. [1] used HumARA typing as a starting point to develop specific formulas for ChrX typing in forensic practice. Therefore, these markers are well established in forensic DNA typing. However, it is known that the HumARA-CAG repeat is located in a coding region (androgen receptor gene, exon 1) and encodes a polyglutamine tract. It has been demonstrated that X-linked spinal and bulbar muscular atrophy (SBMA) is due to a mutation at this locus [2], with trinucleotide repeats more than 43 bp long.

In addition to SBMA disease, HumARA typing may reveal a number of other health risks, including increased risk of impaired spermatogenesis and increased risk of breast, endometrial, colorectal, and prostate cancers.

[1] Desmarais D, Zhong Y, Chakraborty R, Perreault C, Busque L (1998) Development of a highly polymorphic STR marker for identity testing purposes at the human androgen receptor gene (HUMARA). J Forensic Sci 43: 1046-1049.

[2] La Spada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH (1991) Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352: 77-79.

Concluding remarks

We try to operate this site with a high degree of care and scientific responsibility, and intend to accept all submissions that fall within the scope of this site and meet the announced quality standards. In some cases, there may be reasons to reject a submission. In this case the legal process is excluded.